Conjugate heteroatom nucleophile

Conjugate Addition of Heteroatom Nucleophiles and Subsequent Nef Reaction... 

Substitution of complexed dienols (244) or dienol acetates with carbon or heteroatom nucleophiles, in the presence of a Lewis acid, occurs with retention of configuration (Scheme 69). (Alkyl aluminum reagents act as both nucleophile and Lewis acid in this process). This reaction is believed to proceed via stereospecific ionization, with anchimeric assistance from the iron, to generate the transoid pentadienyl cation (247) followed by attack of the weak nucleophile on the face opposite to iron. The cross-conjugated pentadienyl cation can also be generated the substitution of (2-acetoxymethyl-l,3-butadiene)Fe(CO)3 (193) has previously been discussed (Section 6.1.1). 

In the palladium-catalyzed 1,4-oxidations of conjugated dienes described so far, only heteroatom nucleophiles have been employed. There is an intrinsic problem in using free carbanions in an oxidation reaction since the oxidant can readily remove an electron and oxidize the carbanion to a radical. Furthermore, in the procedure associated with the best selectivity, i.e., the benzoquinone-based process, acid is required to regenerate the Pd(0)-benzoquinone complex to Pd(II) and hydroquinone. 

This commoner type of reaction involves the attack of carbon or heteroatom nucleophiles onto carbonyl compounds, by direct or conjugate addition, and onto imines. Because we have just dealt with boranes we shall start with the reaction of allylic boron compounds with such electrophiles. You might strictly not call this nucleophilic attack. 

The term Michael addition has been used to describe 1,4- (conjugate) additions of a variety of nucleophiles including organometallics, heteroatom nucleophiles such as sulfides and amines, enolates, and allylic organometals to so-called Michael acceptors such as a,p-unsaturated aldehydes, ketones, esters, nitriles, sulfoxides, and nitro compounds. Here, the term is restricted to the classical Michael reaction, which employs resonance-stabilized anions such as enolates and azaenolates, but a few examples of enamines are also included because of the close mechanistic similarities. 

The organocatalytic asymmetric conjugate addition of heteroatom nucleophiles to different electrophilic olefins has become a very popular reaction during the last few years. Different nitrogen, oxygen, sulfur, and selenium nucleophilic species have been successfully used leading to enantiomerically emiched heterofunctionalized derivatives. 

Kang and co-workers have reported reactions of open-chain vinyl-substituted cyclic carbonates with many stabilized and nonstabilized carbon nucleophiles,heteroatom nucleophiles, hydride equivalent,and vinyl and aryltin reagents. Retention of configuration has been observed for malonate, for thiophenolate, and for the conjugate base of phthalimide. In the absence of nucleophile a proton elimination ensues (Scheme 44). The reaction with iodobenzene produces a reductive ring opening by a variant of the Heck reaction. ... 

A number of intramolecular Pd-catalyzed 1,4-oxidations of conjugated dienes were developed.f In these reactions, two nucleophiles are added across the diene, one of which adds intramolecularly. So far, only heteroatom nucleophiles have been employed. In order to extend these intramolecular 1,4-oxidations to carbon nucleophiles, it was found that a vinylpalladium species can be obtained in situ from an alkyne via a chloropalladation. The approach is particularly attractive since it involves a Pd(II) chloride salt and could be compatible with the rest of the catalytic cycle. Reaction of dienyne with LiCl, and benzoquinone in the presence of palladium acetate as the catalyst, afforded the carbocyclization products. The reaction resulted in an overall stereoselective fltiri-addition of carbon and chlorine across the diene t B (Scheme 23). 

Functionalization of Conjugated Dienes. Electrophilic transition metals, particularly palladium(II) salts which do not form stable complexes with 1,3-dienes, do activate these substrates to undergo a variety of synthetically useful reactions with heteroatom nucleophiles. Some examples are presented below. 

Asymmetric Conjugate Additions with Heteroatom Nucleophiles... 

In a manner largely complementary to secondary amine-catalyzed asymmetric conjugate addition to enals with heteroatom nucleophiles, chiral primary amines were recently found to be the catalysts of choice for similar Michael addition to a,p-unsaturated ketones. With their previously developed cinchona-type catalyst 91, Melchiorre and coworkers achieved the asymmetric sulfa-Michael addition to a,p-unsaturated ketones with either benzyl or tert-butyl mercaptane (Scheme 5.30) [58a]. The same catalyst could be further extended to oxa-Michael addition to enones by optimizing the ratio of acidic additive and solvents (Scheme 5.30) [58b]. 

In the absence of heteroatom containing substituents (e.g. halo-, cyano-), at or conjugated with the radical center, carbon-centered radicals have nucleophilic character. Thus, simple alkyl radicals generally show higher reactivity toward electron-deficient monomers (eg. acrylic monomers) than towards electron-rich monomers (e.g, VAc, S) - Table 3.6. 

---